Evidence map›Paper›PMID 28490597›Full record

ArticleJournal of virology2017

Molluscum Contagiosum Virus Protein MC005 Inhibits NF-κB Activation by Targeting NEMO-Regulated IκB Kinase Activation.

Gareth Brady, Darya A Haas, Paul J Farrell, Andreas Pichlmair, Andrew G Bowie

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.6field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 43 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Molluscum Contagiosum Virus: Biology and Immune Response.Advances in experimental medicine and biology · 2024
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Rubicon: a facilitator of viral immune evasion.Cellular & molecular immunology · 2019
    Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 3 countries.

Gareth BradySchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland bradyg1@tcd.ie agbowie@tcd.ie.
Darya A HaasMax Plank Institute of Biochemistry, Martinsried, Germany.
Paul J FarrellSection of Virology, Imperial College Faculty of Medicine, Norfolk Place, London, United Kingdom.
Andreas PichlmairMax Plank Institute of Biochemistry, Martinsried, Germany.
Andrew G BowieSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland bradyg1@tcd.ie agbowie@tcd.ie.
Max Planck Institute of Biochemistry · DETrinity College Dublin · IEImperial College London · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Molluscum contagiosum virus (MCV), the only known extant human-adapted poxvirus, causes a long-duration infection characterized by skin lesions that typically display an absence of inflammation despite containing high titers of live virus. Despite this curious presentation, MCV is very poorly characterized in terms of host-pathogen interactions. The absence of inflammation around MCV lesions suggests the presence of potent inhibitors of human antiviral immunity and inflammation. However, only a small number of MCV immunomodulatory genes have been characterized in detail. It is likely that many more remain to be discovered, given the density of such sequences in other poxvirus genomes. NF-κB activation occurs in response to both virus-induced pattern recognition receptor (PRR) signaling and cellular activation by virus-induced proinflammatory cytokines like tumor necrosis factor and interleukin-1. Activated NF-κB drives cytokine and interferon gene expression, leading to inflammation and virus clearance. We report that MC005, which has no orthologs in other poxvirus genomes, is a novel inhibitor of PRR- and cytokine-stimulated NF-κB activation. MC005 inhibited NF-κB proximal to the IκB kinase (IKK) complex, and unbiased affinity purification revealed that MC005 interacts with the IKK subunit NEMO (NF-κB essential modulator). MC005 binding to NEMO prevents the conformational priming of the IKK complex that occurs when NEMO binds to ubiquitin chains during pathway activation. These data reveal a novel mechanism of poxvirus inhibition of human innate immunity, validate current dynamic models of NEMO-dependent IKK complex activation, and further clarify how the human-adapted poxvirus MCV can so effectively evade antiviral immunity and suppress inflammation to persist in human skin lesions.

Indexed as

Host-Pathogen InteractionsImmune EvasionAnimalsCell LineHumansI-kappa B KinaseMolluscum contagiosum virusNF-kappa BViral ProteinsI-kappa B KinaseIKBKG protein, humanNF-kappa BViral Proteinsimmune evasioninnate immunitymolluscum contagiosum virusNF-κBpoxvirus

Identifiers

PMID28490597
PMCPMC5512260
OpenAlexW2612865023

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.